A comparative study of the antipyretic effects of indomethacin and dipyrone in rats
A comparative study of the antipyretic effects of indomethacin and dipyrone in rats
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DOI：
10.1007/pl00000278
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发表时间：
2002-01-01
影响因子：
6.7
通讯作者：
Zampronio, AR
中科院分区：
文献类型：
--
作者：
de Souza, GEP;Cardoso, RA;Zampronio, AR
目的：比较安乃近和吲哚美辛的解热作用。v. LPS或i. C. v.白细胞介素（IL）、白介素（PG）、花生四烯酸（AA）、预形成致热原因子（PFPF）、肿瘤坏死因子-α（TNT-α）或促肾上腺皮质激素释放激素（CRH）。腹腔注射安乃近和吲哚美辛，精氨酸加压素V-1受体拮抗剂d（CH 2）（5）Tyr（Me）AVP注入腹侧隔区。在转染的COS-7细胞中评估环氧合酶（考克斯-1/-2）阻断活性。结果：吲哚美辛和安替比林能减少LPS、IL-1 β、IL-6和TNF-α引起的大鼠发热和下丘脑CRH的释放。仅安乃近抑制IL-8、PFPF或PGF（2 α）发热。只有吲哚美辛抑制AA或IL-1 β加AA引起的发热。解热剂对PGE（2）或CRH引起的发热无影响。d（CH_2）（5）Tyr（Me）AVP仅阻断消炎痛的解热作用。在COS-7细胞中，高浓度（10 mM）的安乃近仅抑制考克斯-1，而吲哚美辛（0.1 μ M）阻断考克斯-1和考克斯-2。结论：安乃近的解热作用与吲哚美辛不同，它不依赖于AVP释放或PG合成的抑制。
Objective: Compare the antipyretic effects of dipyrone and indomethacin.Materials and methods: Fever was induced in rats by i. v. LPS or i. c. v. interleukins (IL), prostaglandins (PG), arachidonic acid (AA), pre-formed pyrogenic factor (PFPF), tumour necrosis factor-alpha (TNT-alpha) or corticotrophin releasing hormone (CRH). Dipyrone and indomethacin were administered i.p., arginine vasopressin V-1-receptor antagonist, d(CH2)(5) Tyr(Me)AVP, into the ventral septal area. Cyclooxygenase (COX-1/-2) blocking activity was assessed in transfected COS-7 cells. CRH release from isolated hypothalami was determined by ELISA.Results: Indomethacin or dipyrone reduced LPS, IL-1beta, IL-6 or TNF-alpha induced fever and CRH release from rat hypothalamus. Only dipyrone inhibited IL-8, PFPF or PGF(2alpha) fever. Only indomethacin inhibited fever induced by AA or IL-1beta plus AA. Neither antipyretic affected fever caused by PGE(2) or CRH. d(CH2)(5)Tyr(Me)AVP only blocked antipyresis induced by indomethacin. Dipyrone at a very high concentration (10 mM) inhibited only COX-1, while indomethacin (0.1 muM) blocked COX-1 and COX-2 in COS-7 cells.Conclusion: The antipyretic effect of dipyrone differs from that of indomethacin in that it does not depend on AVP release or inhibition of PG synthesis.